{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:19:17Z","timestamp":1785403157354,"version":"3.56.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100018694","name":"HORIZON EUROPE Marie Sklodowska-Curie Actions","doi-asserted-by":"publisher","award":["861323"],"award-info":[{"award-number":["861323"]}],"id":[{"id":"10.13039\/100018694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2022-00657"],"award-info":[{"award-number":["2022-00657"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      This study aimed to describe the immune response and activity of the novel antibiotic afabicin against\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      in an immunocompetent mouse thigh infection model using PKPD modeling and to predict the clinical efficacy of different afabicin dosing regimens in\n                      <jats:italic toggle=\"yes\">Staphylococcus<\/jats:italic>\n                      -infected immunocompetent patients. Bacterial counts of five\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      strains were determined over 74 h in an immunocompetent mouse thigh infection model. Afabicin doses of 0.011\u2013150 mg\/kg were administered intraperitoneally every 6 h. A PKPD model was developed to describe immune response and afabicin desphosphono (active moiety) activity. The model was used jointly with a human population PK model for afabicin to predict the efficacy of different clinical dosing regimens (intravenous 55 to 160 mg twice-daily or oral 80 to 240 mg twice-daily) in immunocompetent patients. The developed model included a saturable neutrophil-mediated phagocytosis process of bacteria. The afabicin desphosphono effect was characterized using a model structure previously developed based on\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      time-kill and neutropenic mouse thigh infection data. A lower maximum killing rate constant (0.24 h\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) and an 82% lower EC\n                      <jats:sub>50<\/jats:sub>\n                      were estimated for immunocompetent animals compared to\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Predictions indicated that all tested afabicin regimens would achieve bacterial killing in immunocompetent patients infected with\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      . Afabicin activity against five\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      strains was adequately quantified in immunocompetent animals by the developed PKPD model. Predictions supported the efficacy of afabicin 55 mg intravenously twice daily, followed by an 80 mg oral twice-daily regimen in humans, which is currently tested in a clinical trial in bone and joint infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00959-25","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:11:37Z","timestamp":1772637097000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Model-based quantification of immune response and anti-staphylococcal activity of afabicin in immunocompetent mouse thigh infections to enable predictions of clinical efficacy"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3459-6839","authenticated-orcid":true,"given":"Rapha\u00ebl","family":"Saporta","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy, Uppsala University","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0725-214X","authenticated-orcid":false,"given":"Elisabet I.","family":"Nielsen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy, Uppsala University","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annick","family":"Menetrey","sequence":"additional","affiliation":[{"name":"Translational Medicine Department, Debiopharm International SA","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Translational Medicine Department, Debiopharm International SA","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Nicolas-M\u00e9tral","sequence":"additional","affiliation":[{"name":"Translational Medicine Department, Debiopharm International SA","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2979-679X","authenticated-orcid":true,"given":"Lena E.","family":"Friberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy, Uppsala University","place":["Uppsala, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"European Medicines Agency. 2016. 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